Au début, les réseaux sociaux numériques (RSN) étaient conçus comme étant des moyens purement communicationnels : par exemple, chercher l'ami d'autrefois pour rétablir une communication. Avec cette révolution tentaculaire de la communication horizontale, un autre axe vertical est né : la transmission. Des politiciens (Obama et Facebook lors de la campagne électorale aux USA), des stars, des leaders, des hommes de l'Eglise (Benoit XVI premier pape sur Twitter), etc., ont imposé un nouveau modèle de présence : une transmission verticale, opération par laquelle un signal, un message est acheminé d'un émetteur vers un récepteur ou une masse. La transmission est souvent dépourvue de l'interactivité. C'est le dilemme des RSN : Transmission et communication. Communiquer un message, c'est l'apporté sur un axe horizontal hétérarchique (locuteur/interlocuteur). Transmettre un message, c'est l'apporté sur un axe vertical hiérarchique (émetteur/récepteur).Le message transmis peut confronter l'échec : refus du message, message erroné, faux émetteurs, etc. et au niveau de l'Eglise catholique, notre cas d'étude, l'échec dans la transmission de son message (la foi) peut être destructif : hérésies, sentimentalisme, transmission dangereuse, obsession même diabolique, etc.Comment l'Eglise catholique, avec sa structure hiérarchique, peut établir une transmission réussie : Officielle (sure), acceptable et instructive ? Egalement, comment elle peut respecter et assurer la réconciliation entre les deux piliers des RSN : communication (axe horizontal) et transmission (axe vertical) ? Dans la première partie, nous trouvons une observation du développement du réseau social qui a revêtu, au fur et à mesure, la forme que nous connaissons aujourd'hui, Réseaux Sociaux Numériques (RSN). Dans la deuxième, et après un rappel historique des phases majeures de la formulation de la conception ecclésiale des médias, et une présentation des textes magistraux clés concernant sa vision vis-à-vis des RSN, une interview avec l'administrateur d'un groupe ecclésial sur les RSN (un modèle type) et un questionnaire dirigé aux membres, seront faits dans le but de révéler des directives et des éclaircissements qui dessinent le fil conducteur de la dernière partie de la thèse. Une nouveauté est présentée à la dernière partie : une nouvelle stratégie de transmission 2.0 constituée de différentes propositions : - Des transformations préalables au sein de l'Eglise dans sa vision du monde des RSN : les RSN sont une occasion posée par la parenté des deux axes : vertical et horizontal. - Etablir une institution officielle et des bureaux RSN ecclésiastiques pour gérer les groupes certifiés. - Une collaboration bureautique et technique entre : Eglise et Entreprises RSN (facebook, Twitter, Google +, etc.).-Esquisse d'un wiki-manuel : document officiel qui constitue un «open source», il met les directives générales de la transmission 2.0 de l'Eglise. / At first, the digital social networks (DSN) were understood as communicational means: example, search an old friend in order to create a communication. With this tentacular revolution of this horizontal communication, another vertical axe was born: the transmission. Politicians (Obama and Facebook during the electoral campaign at the USA), stars, leaders, Men of the Church (Benoit XVI first Pope at Twitter), etc. imposed a new sample of presence: a vertical transmission, a process where a signal, a message is moving towards from a transmitter to a receiver or to a mass. The transmission is often devoid of interactivity. It's the dilemma of the DSN: Transmission and communication. To communicate a message means to bring it on a horizontal axe (speaker/interlocutor). To transmit a message means to bring it on hierarchic vertical axe (transmitter/receiver).The transmitted message may fail: refusal of the message, wrong message, wrong transmitters, etc. As for the Catholic Church, our case study, the failure in the transmission of its message (the faith) may be destroying: heresy, sentimentalism, dangerous transmission, obsession even devilish, etc.How a Catholic Church, with its hierarchic structure, can set up a successful transmission: Official (sure), acceptable and instructive? How a Catholic Church can respect and assure the reconciliation between the two pillars of the DSN: Communication (horizontal axe) and transmission (vertical axe)?In the first part, we find an observation of the development of the social network that has taken on, as one goes along, the shape that we know nowadays, Digital Social Networks (DSN). In the second part, and after a historical summary of the major stages of the formulation of the medias church conception, and a presentation of the key masterly texts concerning its vision towards DSN, an interview with the administrator of the ecclesiastic group about the DSN (a sample) and a questionnaire addressed to the members will be achieved in order to reveal instructions and explanations that draw the vital lead of the last part of the thesis.A novelty is presented in the last part: a new strategy of transmission 2.0 that is constituted of different propositions:-Prior transformations in the bosom of the Church in its view of the DSN world: The DSN are an occasion created from the relationship of the two axes: vertical and horizontal.-To establish an official institution and ecclesiastical DSN offices in order to manage the certified groups.-A technical and office automation collaboration between: Church and DSN firms (Facebook, Twitter, Google + etc).-An outline of a wiki-manual: an official document that constitutes an “open source” it sets up the general instructions of the transmission 2.0 of the Church.

<p>Es que la política puede ser interpretada como una guerra? Así es considerada por Foucault y en esa orientación, el objetivo de este ensayo es aproximarse teóricamente al tema del poder en tanto efecto de verdad en los discursos filosófico- jurídico e histórico- político. En el primer caso, el poder, dentro del discurso filosófico-jurídico, es una atribución legítima del Estado y su verdad está basada en la soberanía del pueblo, en el segundo caso, el poder se traduce en una guerra constante, en que la lucha y la victoria proporcionan la verdad. En este contexto, se averigua sobre el poder en los extremos capilares donde es una fuerza que no hace uso de las leyes, para el caso de la dictadura militar en Chile 1973-1989</p><p>.La Operación Cóndor es una de esas manifestaciones del poder en el extremo capilar. Entre las víctimas de este poder encontramos las voces que sometidas por esta represión, expresan en discursos aislados y fragmentarios, la defensa de los derechos conculcados a los chilenos en general. Los discursos a que nos referimos en este estudio, se desarrollaban en Italia, Francia, Argentina y Estados Unidos. Estas voces que son portadoras de discursos de soberanía del pueblo, no son parte de un Sujeto en un supra texto como sería la expresión de una clase social derrotada por otra en la conceptualización marxista, son gestos, expresiones en individuos que participan de un discurso que sobrevive temporalmente a la destrucción de la democracia que defienden y el estado protector en Chile. La conjunción de la ciencia con el saber de la gente, en este caso las voces de los saberes sometidos, de la historia oprimida y el redescubrimiento conjunto de la lucha y memoria directa de los enfrentamientos, constituye una genealogía en la teoría de Foucault, hacer esta distinción en la historia posibilita un descentramiento de los saberes que permite la descripción de aspectos que han quedado en silencio en la ciencia política e histórica.</p>

Es que la política puede ser interpretada como una guerra? Así es considerada por Foucault y en esa orientación, el objetivo de este ensayo es aproximarse teóricamente al tema del poder en tanto efecto de verdad en los discursos filosófico- jurídico e histórico- político. En el primer caso, el poder, dentro del discurso filosófico-jurídico, es una atribución legítima del Estado y su verdad está basada en la soberanía del pueblo, en el segundo caso, el poder se traduce en una guerra constante, en que la lucha y la victoria proporcionan la verdad. En este contexto, se averigua sobre el poder en los extremos capilares donde es una fuerza que no hace uso de las leyes, para el caso de la dictadura militar en Chile 1973-1989 .La Operación Cóndor es una de esas manifestaciones del poder en el extremo capilar. Entre las víctimas de este poder encontramos las voces que sometidas por esta represión, expresan en discursos aislados y fragmentarios, la defensa de los derechos conculcados a los chilenos en general. Los discursos a que nos referimos en este estudio, se desarrollaban en Italia, Francia, Argentina y Estados Unidos. Estas voces que son portadoras de discursos de soberanía del pueblo, no son parte de un Sujeto en un supra texto como sería la expresión de una clase social derrotada por otra en la conceptualización marxista, son gestos, expresiones en individuos que participan de un discurso que sobrevive temporalmente a la destrucción de la democracia que defienden y el estado protector en Chile. La conjunción de la ciencia con el saber de la gente, en este caso las voces de los saberes sometidos, de la historia oprimida y el redescubrimiento conjunto de la lucha y memoria directa de los enfrentamientos, constituye una genealogía en la teoría de Foucault, hacer esta distinción en la historia posibilita un descentramiento de los saberes que permite la descripción de aspectos que han quedado en silencio en la ciencia política e histórica.

The Deep Space Network (DSN), located at the Jet Propulsion Laboratory (JPL), is developing an RF/Optical Hybrid Antenna. This antenna concept will support the reception of high-bandwidth optical deep-space communications with simultaneous support of conventional RF uplink and downlink. The optical system on the antenna consists of sixty-four hexagonal mirrors positioned to form a spherical aperture. To align the mirrors, a Position Opto-Electronic Metrology Sensor (POEMS) system is used to measure the position of each mirror relative to one another. The POEMS system consists of a sender called a collimator, which sends collimated light to the receiving component, called a quadrant diode. The purpose of this thesis is to gain insight into the required range of the POEMS system through a Monte Carlo stack-up tolerance analysis. Misalignments and tolerances may exceed current hardware capabilities of 0.3 mm. Furthermore, this thesis aims to understand the impacts of each tolerance through sensitivity analysis. The mathematical model of the mirror assembly, the Monte Carlo, and sensitivity analysis were modeled in MATLAB. The Monte Carlo analysis in this thesis takes a random value from a probability distribution of each tolerance. Then, the analysis calculates where the intersection of the representative collimator beam on its respective quadrant diode occurs. The analysis repeats this for the desired number of random stack-up of the tolerances. The maximum pointing error obtained from the Monte Carlo simulations is 6.003 mm. The tolerances which have the most considerable effect on pointing error are the decenter (which has the most significant impact), clocking, wedge, and mirror thickness. These are the tolerances to minimize if the hardware cannot be improved to meet the required range.

A visualization of the NASA Deep Space Network activity. Implemented in an interactive 3D environment. A thesis work by students from the Media technology and engineering program at Linköping University.

International Telemetering Conference Proceedings / October 26-29, 1998 / Town & Country Resort Hotel and Convention Center, San Diego, California / The Near Earth Asteroid Prospector (NEAP) has a scheduled launch date between mid- 1999 and mid-2000, and will encounter a yet to be determined near Earth asteroid (1.1 - 2.2 AU distance from Earth) some ten months later [2]. The purpose of this mission is not only to collect valuable scientific and geological data, but to also determine the value of the asteroid’s materials for possible mining and exploitation [2], [3]. The purpose of this paper is to detail frequency allocation issues and to determine possible return (space to Earth) data rates associated with deep space communications with the NEAP spacecraft.

Em 31 de março de 1964, um golpe civil-militar depôs o presidente João Belchior Marques Goulart (7 de Setembro de 1961 a 1º de abril de 1964), iniciando um ciclo de aproximadamente vinte e um anos de ditadura militar no Brasil (1º de abril de 1964 a 15 de março de 1985), durante o qual o comando do Poder Executivo foi exercido por generais do exército, inspirados pela Doutrina de Segurança Nacional (DSN). Concebida na Escola Superior de Guerra (ESG), essa orientação ostentava forte conotação geopolítica e ancorava-se no binômio segurança e desenvolvimento, que tinha como pressupostos fundamentais a busca pelo acelerado desenvolvimento econômico e a segurança do país contra a ação de supostos agentes subversivos vinculados ao comunismo internacional. Os governos militares também acreditavam na possibilidade de transformar a nação em uma potência capaz de exercer plena liderança na América do Sul e em sua área atlântica, concretizando, assim, uma antiga aspiração nacional: a construção do Brasil Potência. O golpe de 1964, que chegou a ser considerado a principal batalha da Guerra Fria, contou com forte apoio ideológico e material dos Estados Unidos da América, inaugurando uma importante parceria entre os dois países, com o objetivo de barrar qualquer possibilidade de avanço das propostas de esquerda no continente latino-americano. Para os formuladores da ESG, tal comunhão de interesses já estava delineada, pois o Brasil, enquanto país ocidental, cristão e democrático, deveria cerrar fileiras com a maior potência do mundo capitalista no projeto de contenção ao comunismo. Tal associação terá inevitável reflexo na condução da política externa brasileira. O objetivo desta dissertação é investigar e compreender a ação internacional e a política externa do Brasil durante os três primeiros governos do regime militar (1964-1973), especialmente as gestões de Costa e Silva e Emílio Médici, com ênfase na construção do sistema de informação e repressão aos movimentos sociais e políticos de oposição, nas intervenções do país nos assuntos internos das nações vizinhas, em seus vínculos com os Estados Unidos da América e a na centralidade do grupo militar que ocupa a liderança do Poder Executivo na definição e na formulação desses objetivos. / In March 31, 1964, a civil-military coup détat ousted the Brazilian president João Belchior Marques Goulart (his administration began in September 7, 1961 and finished in April 1, 1964), starting a period of about twenty one years of military dictatorship in Brazil (since April 1, 1964 up to March 15, 1985), in which the presidency was occupied by a sequence of generals, inspired by National Security Doctrine. Devised by Superior War School (ESG, an institution comparable to the American National War College) and structured under geopolitical concepts, the National Security Doctrine was based on a binomial expression development and security which enveloped the quest for rapid economic development and a concern for national security against subversive agents from international communism. The military governments also believed in the possibility of transforming the country into a power able to exercise full leadership in South America and its Atlantic area, realizing thus an old national aspiration: the construction of Brasil Potência (Brazil Power). The coup détat in Brazil, an event that is often considered the most important battle within the Cold War, had strong material and ideological support from the United States, and started an important partnership between the two countries in order to block any possibility of success to leftist ideas in Latin-America. To ESGs policy makers, an US-Brazil alliance was given, since Brazil as a Western, Christian and democratic country, should be a partner with the U.S. in the fight against communism. This association is inevitably reflected in the conduct of Brazilian foreign policy. The aim of this dissertation is to investigate and understand Brazils international posture and foreign policy during the first three governments of the military regime (1964-1973) especially the Costa e Silva and Emílio Médici administrations. The dissertation covers the construction of the information system and the repression of social movements and opposition politicians, as well as the Brazilian intervention in the internal affairs of neighboring nations, its ties with the United States and the centrality of the small cadre that led the executive branch in the definition and formulation of these objectives.

Em 31 de março de 1964, um golpe civil-militar depôs o presidente João Belchior Marques Goulart (7 de Setembro de 1961 a 1º de abril de 1964), iniciando um ciclo de aproximadamente vinte e um anos de ditadura militar no Brasil (1º de abril de 1964 a 15 de março de 1985), durante o qual o comando do Poder Executivo foi exercido por generais do exército, inspirados pela Doutrina de Segurança Nacional (DSN). Concebida na Escola Superior de Guerra (ESG), essa orientação ostentava forte conotação geopolítica e ancorava-se no binômio segurança e desenvolvimento, que tinha como pressupostos fundamentais a busca pelo acelerado desenvolvimento econômico e a segurança do país contra a ação de supostos agentes subversivos vinculados ao comunismo internacional. Os governos militares também acreditavam na possibilidade de transformar a nação em uma potência capaz de exercer plena liderança na América do Sul e em sua área atlântica, concretizando, assim, uma antiga aspiração nacional: a construção do Brasil Potência. O golpe de 1964, que chegou a ser considerado a principal batalha da Guerra Fria, contou com forte apoio ideológico e material dos Estados Unidos da América, inaugurando uma importante parceria entre os dois países, com o objetivo de barrar qualquer possibilidade de avanço das propostas de esquerda no continente latino-americano. Para os formuladores da ESG, tal comunhão de interesses já estava delineada, pois o Brasil, enquanto país ocidental, cristão e democrático, deveria cerrar fileiras com a maior potência do mundo capitalista no projeto de contenção ao comunismo. Tal associação terá inevitável reflexo na condução da política externa brasileira. O objetivo desta dissertação é investigar e compreender a ação internacional e a política externa do Brasil durante os três primeiros governos do regime militar (1964-1973), especialmente as gestões de Costa e Silva e Emílio Médici, com ênfase na construção do sistema de informação e repressão aos movimentos sociais e políticos de oposição, nas intervenções do país nos assuntos internos das nações vizinhas, em seus vínculos com os Estados Unidos da América e a na centralidade do grupo militar que ocupa a liderança do Poder Executivo na definição e na formulação desses objetivos. / In March 31, 1964, a civil-military coup détat ousted the Brazilian president João Belchior Marques Goulart (his administration began in September 7, 1961 and finished in April 1, 1964), starting a period of about twenty one years of military dictatorship in Brazil (since April 1, 1964 up to March 15, 1985), in which the presidency was occupied by a sequence of generals, inspired by National Security Doctrine. Devised by Superior War School (ESG, an institution comparable to the American National War College) and structured under geopolitical concepts, the National Security Doctrine was based on a binomial expression development and security which enveloped the quest for rapid economic development and a concern for national security against subversive agents from international communism. The military governments also believed in the possibility of transforming the country into a power able to exercise full leadership in South America and its Atlantic area, realizing thus an old national aspiration: the construction of Brasil Potência (Brazil Power). The coup détat in Brazil, an event that is often considered the most important battle within the Cold War, had strong material and ideological support from the United States, and started an important partnership between the two countries in order to block any possibility of success to leftist ideas in Latin-America. To ESGs policy makers, an US-Brazil alliance was given, since Brazil as a Western, Christian and democratic country, should be a partner with the U.S. in the fight against communism. This association is inevitably reflected in the conduct of Brazilian foreign policy. The aim of this dissertation is to investigate and understand Brazils international posture and foreign policy during the first three governments of the military regime (1964-1973) especially the Costa e Silva and Emílio Médici administrations. The dissertation covers the construction of the information system and the repression of social movements and opposition politicians, as well as the Brazilian intervention in the internal affairs of neighboring nations, its ties with the United States and the centrality of the small cadre that led the executive branch in the definition and formulation of these objectives.

Cytotoxic T-lymphocytes (CTLs) are important components of the adaptive immune system and function by scanning the intracellular environment so as to detect and de-stroy infected cells. CTL responses play a major role in controlling virus-infected cells such as in HIV or influenza and cells infected with intracellular bacteria such as in tuberculosis. To do so they require the antigens to be presented to them, which is fulfilled by the major histocompatibility complex (MHC), commonly known as human leukocyte antigen or HLA molecules in humans. Recognition of antigenic peptides to Class-1 HLA molecules is a prerequisite for triggering CTL immune responses. Individuals differ significantly in their ability to respond to an infection. Among the factors that govern the outcome of an infection, HLA polymorphism in the host is one of the most important. Despite a large body of work on HLA molecules, much remains to be understood about the relationship between HLA diversity and disease susceptibility. High complexity arises due to HLA allele polymorphism, extensive antigen cross-presentability, and host-pathogen heterogeneity. A given allele can recognize a number of different peptides from various pathogens and a given peptide can also bind to a number of different individuals. Thus, given the plurality in peptide-allele pairs and the large number of alleles, understanding the differences in recognition profiles and the implications that follow for disease susceptibilities require mathematical modelling and computational analysis. The main objectives of the thesis were to understand heterogeneity in antigen presentation by HLA molecules at different scales and how that heterogeneity translates to variations in disease susceptibilities and finally the disease dynamics in different populations. Towards this goal, first the variations in HLA alleles need to be characterized systematically and their recognition properties understood. A structure-based classification of all known HLA class-1 alleles was therefore attempted. In the process, it was also of interest to see if understanding of sub-structures at the binding grooves of HLA molecules could help in high confidence prediction of epitopes for different alleles. Next, the goal was to understand how HLA heterogeneity affect disease susceptibilities and disease spread in populations. This was studied at two different levels. Firstly, modelling the HLA genotypes and CTL responses in different populations and assessing how they recognized epitopes from a given virus. The second approach involved modelling the disease dynamics given the predicted susceptibilities in different populations. Influenza H1N1 infection was used as a case study. The specific objectives addressed are: (a) To develop a classification scheme for all known HLA class-1 alleles that can explain epitope recognition profiles and further to dissect the physic-chemical features responsible for differences in peptide specificities, (b) A statistical model has been derived from a large dataset of HLA-peptide complexes. The derived model was used to identify the interdependencies of residues at different peptide and thereby, rationalize the HLA class-I allele binding specificity at a greater detail, (c) To understand the effect of HLA heterogeneity on CTL mediated disease response. A model of HLA genotypes for different populations was required for this, which was constructed and used for estimating disease response to H1N1 via the prediction of epi-topes and (d) To model disease dynamics in different populations with the knowledge of the CTL response-grouping and to evaluate the effect of heterogeneity on different vaccination strategies. Each of the four objectives listed above are described subsequently in chapters 2 to 5, followed by Chapter 6 which summarises the findings from the thesis and presents future directions. Chapter 1 presents an introduction to the importance of the function of HLA molecules, describes structural bioinformatics as a discipline and the methods that are available for it. The chapter also describes different mathematical modelling strategies available to study host immune responses. Chapter 2 describes a novel method for structure-based hierarchical classification of HLA alleles. Presently, more than 2000 HLA class-I alleles are reported, and they vary only across peptide-binding grooves. The polymorphism they exhibit, enables them to bind to a wide range of peptide antigens from diverse sources. HLA molecules and peptides present a complex molecular recognition pattern due to multiplicity in their associations. Thus, a powerful grouping scheme that not only provides an insightful classification, but is also capable of dissecting the physicochemical basis of recognition specificity is necessary to address this complexity. The study reports a hierarchical classification of 2010 class-I alleles by using a systematic divisive clustering method. All-pair distances of alleles were obtained by comparing binding pockets in the structural models. By varying the similarity thresholds, a multilevel classification with 7 supergroups was derived, each further categorized to yield a total of 72 groups. An independent clustering scheme based only on the similarities in their epitope pools correlated highly with pocket-based clustering. Physicochemical feature combinations that best explains the basis for the observed clustering are identified. Mutual information calculated for the set of peptide ligands enables identification of binding site residues that contribute to peptide specificity. The grouping of HLA molecules achieved here will be useful for rational vaccine design, understanding disease susceptibilities and predicting risk of organ transplants. The results are presented in an interactive web- server http://proline.iisc.ernet.in/hlaclassify. In Chapter 3, the knowledge of structural features responsible for generating peptide recognition specificities are first analysed and then utilized for predicting T-cell epi-topes for any class-1 HLA allele. Since identification of epitopes is critical and central to many of the questions in immunology, a study of several HLA-peptide complexes is carried out at the structural level and factors are identified that discriminate good binder peptides from those that do not. T-cell epitopes serve as molecular keys to initiate adaptive immune responses. Identification of T-cell epitopes is also a key step in rational vaccine design. Most available methods are driven by informatics, critically dependent on experimentally obtained training data. Analysis of the training set from IEDB for several alleles indicate that sampling of the peptide space is extremely sparse covering only a tiny fraction of all possible nonamer space, and also heavily skewed, thus restricting the range of epitope prediction. A new epitope prediction method is therefore developed. The method has four distinct modules, (a) structural modelling, estimating statistical pair-potentials and constraint derivation, (b) implicit modelling and interaction profiling, (c) binding affinity prediction through feature representation and (d) use of graphical models to extract peptide sequence signatures to predict epitopes for HLA class I alleles . HLaffy is a novel and efficient epitope prediction method that predicts epitopes for any HLA Class-1 allele, by estimating binding strengths of peptide-HLA complexes which is achieved through learning pair-potentials important for peptide binding. It stands on the strength of mechanistic understanding of HLA-peptide recognition and provides an estimate of the total ligand space for each allele. The method is made accessible through a webserver http://proline.biochem.iisc.ernet.in/HLaffy. In chapter 4, the effect of genetic heterogeneity on disease susceptibilities are investigated. Individuals differ significantly in their ability to respond to an infection. Among the factors that govern the outcome of an infection, HLA polymorphism in the host is one of the most important. Despite a large body of work on HLA molecules, much remains to be understood about how host HLA diversity affects disease susceptibilities. High complexity due to polymorphism, extensive cross-presentability among HLA alleles, host and pathogen heterogeneity, demands for an investigation through computational approaches. Host heterogeneity in a population is modelled through a molecular systems approach starting with mining ‘big data’ from literature. The in-sights derived through this is used to investigate the effect of heterogeneity in a population in terms of the impact it makes on recognizing a pathogen. A case study of influenza virus H1N1 infection is presented. For this, a comprehensive CTL immunome is defined by taking a consensus prediction by three distinct methods. Next, HLA genotypes are constructed for different populations using a probabilistic method. Epidemic incidences in general are observed to correlate with poor CTL response in populations. From this study, it is seen that large populations can be classified into a small number of groups called response-types, specific to a given viral strain. Individuals of a response type are expected to exhibit similar CTL responses. Extent of CTL responses varies significantly across different populations and increases with increase in genetic heterogeneity. Overall, the study presents a conceptual advance towards understanding how genetic heterogeneity influences disease susceptibility in individuals and in populations. Lists of top-ranking epitopes and proteins are also derived, ranked on the basis of conservation, antigenic cross-reactivity and population coverage, which pro- vide ready short-lists for rational vaccine design (flutope). Next, in Chapter 5, the effect of genetic heterogeneity on disease dynamics has been investigated. A mathematical framework has been developed to incorporate the heterogeneity information in the form of response-types described in the previous chap-ter. The spread of a disease in a population is a complex process, controlled by various factors, ranging from molecular level recognition events to socio-economic causes. The ‘response-typing’ described in the previous chapter allows identification of distinct groups of individuals, each with a different extent of susceptibility to a given strain of the virus. 3 different approaches are used for modelling: (i) an SIR model where different response types are considered as partitions of each S, I and R compartment. Initially SIR models are developed, such that the S compartment is sub-divided into further groups based on the ‘response-types’ obtained in the previous chapter. This analysis shows an effect in infection sweep time, i.e., how long the infection stays in the population. A stochastic model incorporates the environmental noise due to random variation in population influx, due to birth, death or migration. The system is observed to show higher stability in the presence of genetic heterogeneity. As the contagion spreads only through direct host to host contact. The topology of the contact network, plays major role in deciding the extent of disease dynamics. An agent based computational framework has been developed for modelling disease spread by considering spatial distribution of the agents, their movement patterns and resulting contact probabilities. The agent-based model (ABM) incorporates the temporal patterns of contacts. The ABM is based on a city block model and captures movement of individuals parametrically. A new concept of system ‘characteristic time’ has been introduced in context of a time-evolving network. ‘Characteristic time’ is the minimum time required to ensure, every individual is connected to all other individuals, in the time aggregated contact network. For any given temporal system, disease time must exceed ‘characteristic time’ in order to spread throughout the population. Shorter ‘characteristic time’ of the system is suggestive of faster spread of the disease. A disease spread network is constructed which shows how the disease spreads from one infected individual to others in the city, given the contact rules and their relative susceptibilities to that viral strain. A high degree of population heterogeneity is seen to results in longer disease residence time. Susceptible individuals preferentially get infected first thereby exposing more susceptible individuals to the disease. Vaccination strategies are derived from the model, which indicates that vaccinating only 20% of the agents, who are hub nodes or highly central nodes and who also have a high degree to susceptible agents, lead to high levels of herd immunity and can confer protection to the rest of the population. Overall, the thesis has provided biologically meaningful classification of all known HLA class-1 alleles and has unravelled the physico-chemical basis for their peptide recognition specificities. The thesis also presents a new algorithm for estimating pep-tide binding affinities and consequently predicting epitopes for all alleles. Finally the thesis presents a conceptual advance in relating HLA diversity to disease susceptibilities and explains how different populations can respond differently to a given infection. A case study with the influenza H1N1 virus identified populations who are most susceptible and those who are least susceptible, in the process identifying important epitopes and responder alleles, providing important pointers for vaccine design. The influence of heterogeneity and response-typing on disease dynamics is also presented for influenza H1N1 infection, which has led to the rational identification of effective vaccination strategies. The methods and concepts developed here are fairly generic and can be adapted easily for studying other infectious diseases as well. Three new web-resources, a) HLAclassify, b) HLaffy and c) Flutope have been developed, which host pre-computed results as well as allow interactive querying to an user to perform analysis with a specific allele, peptide or a pathogenic genome sequence.